Beckwith‐Wiedemann syndrome with Hirschsprung's disease and Meckel's diverticulum

Beckwith-Wiedemann syndrome (BWS) is a rare genomic disorder impacting multiple bodily systems. BWS is characterized by three primary features: overgrowth, macroglossia, and abdominal wall defects, including omphalocele, rectus abdominis dissection, and umbilical hernia.1 Additionally, although rare, there have been documented cases of Hirschsprung's disease associated with BWS.1, 2 Here, we present a case of BWS associated with both Hirschsprung's disease and Meckel's diverticulum. Our patient was a 4-year-old boy diagnosed with BWS. He was delivered via cesarean section, following a full-term pregnancy to non-consanguineous parents. With suggestive clinical features: overgrowth, macroglossia, rectus abdominis dissection, and congenital hyperinsulinism, genetic analysis for BWS was performed, confirming abnormal methylation gain within the imprinting center 1 domain on chromosome 11p15. The abnormality was identified by methylation-specific multiplex ligation-dependent probe amplification in the H19 differentially methylated region. Subsequently, the patient underwent tracheostomy and gastrostomy procedures to address oral intake and respiratory difficulties resulting from macroglossia. Meconium excretion occurred without delay, and defecation was managed with enemas, but the defecation disorder worsened gradually with increased food intake. At 47 months, the patient presented to our outpatient department with complaints of severe constipation. X-ray imaging revealed dilated bowel loops (Figure 1a), and contrast X-rays demonstrated a caliber change at the rectosigmoid junction (Figure 1b). Rectal mucosal biopsy confirmed the absence of ganglion cells in the submucosal layer, with increased acetylcholinesterase-positive fibers, which was highly indicative of Hirschsprung's disease (Figure 1c). At 51 months of age, the patient underwent a laparoscopy-assisted transanal endorectal pull-through (TAEPT) procedure for Hirschsprung's disease. The procedure involved making a mucosal incision 5 mm proximal to the anorectal line, followed by submucosal dissection extending proximally along the rectal wall to the level of the peritoneal reflection. The GelPOINT® Mini Advanced Access Platform (Applied Medical, Rancho Santa Margarita, CA, USA) device was inserted through the umbilical incision, and laparoscopic operation was performed. Confirmation of the transition zone was achieved through a biopsy of the sigmoid-descending junction. Following the transection of the dilated bowel, pull-through anastomosis was successfully performed. During the operation, an additional finding included a Meckel's diverticulum located in the ileum (Figure 1d). Wedge-shaped partial resection of the Meckel's diverticulum was performed. The patient commenced oral feeding on postoperative day 2 and was discharged 16 days after surgery, experiencing a favorable postoperative recovery. Hirschsprung's disease is a well-established congenital motility disorder characterized by functional bowel obstruction, which occurs because of the absence of enteric ganglion cells.3 The disease has been documented in association with various syndromes, such as trisomy 21, Bardet-Biedl syndrome, congenital central hypoventilation syndrome, familial dysautonomia, Shprintzen-Goldberg syndrome, MEN 2A and MEN 2B syndromes, and Smith-Lemli-Opitz syndrome.4 There have been occasional reports of Hirschsprung's disease with BWS1, 2; three in total, including our case. The genetic association between these two diseases has never been described, to our knowledge, and it remains unclear whether BWS combined with Hirschsprung's disease is syndromic. Suita et al.5 reported the rate of Meckel's diverticulum in Hirschsprung's disease as 0.3%–0.5%. In our case, there were no suggestive findings of Meckel's diverticulum in the preoperative examination. This condition was discovered incidentally by careful observation of the small intestine, intraoperatively. Recently, minimally invasive surgeries, including laparoscopic operation and TAEPT have become popular as definitive operations for Hirschsprung's disease. It is important to be aware of the possibility of hidden incidental findings, such as Meckel's diverticulum, even during minimally invasive surgery. In children with BWS, it is important to not only monitor and manage hypoglycemia and screen for embryonal tumors, but also to consider gastrointestinal evaluations for potential congenital organic conditions, such as Hirschsprung's disease and Meckel's diverticulum. Early investigation is recommended, especially in cases that show resistance to drug treatments or are poorly controlled. As similar case reports are published, clear genetic links between Hirschsprung's disease and BWS may become apparent. A.F, T.K., N.K., and K.N. managed the patient's care. A.F. wrote the manuscript. K.Y. provided useful comments for revised manuscript. T.M. and T.T. critically reviewed the manuscript. All authors read and approved the final manuscript. Written informed consent was obtained from the patient's guardian. We thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. The authors declare no conflict of interest.